PROJECT ABSTRACT With advances in treatment and care,a longer life expectancy is changing the demographics of the HIV epidemic, and nearly half of those living with HIV in the U.S. are now 50 years or older. People living with HIV, even while receiving effective HIV medications, have excess morbidity and mortality compared to HIV- uninfected populations. Increasing age, comorbid burden, and lifestyle factors, contribute to greater than expected impairments in key components of daily function and a high burden of fatigue among older adults living with HIV. Effective, scalable, non-pharmacological strategies are needed to improve the healthspan of this vulnerable population. The overall goals of this proposal are to determine whether high-intensity interval training (HIIT) can overcome 1) physical function impairments and increased fatigue and 2) impairments in mitochondrial bioenergetics of older people with HIV (PWH) to a greater extent than continuous moderate-intensity exercise (CME). We further seek to determine whether a biobehavioral coaching intervention following either HIIT or CME can promote long-term adherence to physical activity, a crucial component of the sustainability of the intervention. We have previously demonstrated greater than expected impairments in physical function and a high prevalence of fatigue among older adults with HIV. We found that CME and resistance exercise improves physical function in older PWH, with additional improvements from a higher-intensity aerobic and resistance exercise program. Additionally, only our higher-intensity continuous aerobic exercise intervention reduced fatigue among PWH. Lastly, less than half of our participants continued to exercise at least once a week following the supervised intervention, which suggests that even when exercise is beneficial it can be difficult for PWH to maintain. Together, our findings suggest that an innovative approach to exercise is needed to improve physical function, reduce fatigue, and to maintain a long-term exercise habit among older PWH. To address this critical need, our proposed study will leverage the resources of two diverse participant populations at the University of Colorado and Case Western Reserve University to 1) Compare HIIT vs CME on physical function and fatigue, 2) Compare HIIT vs CME on skeletal muscle and peripheral blood mononuclear cell mitochondrial bioenergetics, and 3) Test a coaching intervention vs control on physical activity adherence, assessing perceptions of these approaches using mixed methods. This study will generate rigorous data on physical function and fatigue responses to exercise, the associated mitochondrial adaptations, and investigate strategies to instill sustained, self-directed exercise behavior. Overall, our findings will inform the development of scalable, effective exercise recommendations tailored to the unique needs of aging PWH.